This is a wastewater-based epidemiology study using wastewater samples that were collected weekly or twice a week from three sewersheds in South Carolina, USA, between either May 27 or June 16, 2020, and Aug 25, 2020, and tested for SARS-CoV-2 RNA. We developed a susceptible-exposed-infectious-recovered (SEIR) model based on the mass rate of SARS-CoV-2 RNA in the wastewater to predict the number of infected individuals, and have also provided a simplified equation to predict this. Model predictions were compared with the number of confirmed cases. We found that the SEIR model provides a robust method to estimate the total number of infected individuals in a sewershed on the basis of the mass rate of RNA copies released per day.

Based on data collected till December 7, 2021, we showed the exponential growth of the Omicron variant over the four-week period in Gauteng (November 8-December 5, 2021) with the doubling time equal 3.38 day [CI 95%: 3.18-3.61 day]. Log-linear regression suggests that the spread began around October 10, 2021, however due to stochasticity in the initial spread this estimate is likely inaccurate. Phylogenetic analysis indicates that the Omicron strain started to diverge in between October 28 and November 5, 2021. This implies that the hidden spread of Omicron before October 10, 2021 (which would suggest slower strain growth) is unlikely. The very short doubling time of Omicron in Gauteng, a province that has reached herd immunity to the Delta variant suggests that Omicron will cause abrupt outbreaks of COVID-19 epidemics across the world, and will become the (temporarily) dominant strain.

Using a broad PheWAS approach in a large discovery and validation cohort, we have identified novel phenotypic associations with risk alleles for severe COVID-19 infection. Interestingly, the ABO locus was associated with comorbidities that are also risk factors for severe COVID-19 infection, suggesting that this locus has pleiotropic effects and provides a potential mechanism for this association. The 19p13 locus was associated with lower risk of autoimmune disease, these findings may have broad implications for the importance of multiple comorbidities across both infectious and non-infectious diseases and may provide insight in the molecular function of the genes near these genetic risk loci.

We used national population data to estimate the household transmissibility of the SARS-CoV-2 lineage B.1.1.7 compared with other lineages. We utilized detailed administrative register data comprising the full Danish population and the ability to link data across registers on a person level. This combined with a large proportion of the population being tested, a large national WGS capacity, and an understanding of the sampling selection process, allowed us to estimate the household transmissibility controlling for age and viral load. We found that B.1.1.7 had a household transmissibility 1.5–1.7 times higher compared with other lineages circulating at the time of the study.

Using isolates of SARS-CoV-2 WT, Beta, Delta and most importantly Omicron we studied the capability of the BNT162b2 vaccine given in two or three doses to neutralize major SARS-CoV-2 variants of concern (VOC). We demonstrate low neutralization efficiency against delta and wild-type for vaccines with more than 5 months following the second BNT162b2 dose, with no neutralization efficiency against Omicron. We demonstrate the importance of a third dose, by showing a 100-fold increase in neutralization efficiency of Omicron following a third dose, with a 4-fold reduced neutralization compared to that against the Delta VOC. The durability of the effect of the third dose is yet to be determined.

Given omicron potential to escape vaccine-induced humoral immunity, we measured neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-12 months), or recently boosted, and accounted for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinated individuals. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is significantly more infectious than any other variant tested.

We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1?million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28?days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1?million vaccinated in the 28?days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1?million patients in the 28?days following a SARS-CoV-2 positive test.

We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunization with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. We found that primary immunization with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.

We show that, with first-generation SARS-CoV-2 vaccines and limited physical distancing in place, the threshold for Omicrons future dominance will primarily be driven by its degree of infectivity. However, Omicrons potential dominance may not necessarily lead to increased public health burden. Expanded vaccination that includes a third-dose for adults and child vaccination strategies is projected to have the biggest public health benefit for a highly infective, highly severe variant with low immune evasion capacity.

This is a wastewater-based epidemiology study using wastewater samples that were collected weekly or twice a week from three sewersheds in South Carolina, USA, between either May 27 or June 16, 2020, and Aug 25, 2020, and tested for SARS-CoV-2 RNA. We developed a susceptible-exposed-infectious-recovered (SEIR) model based on the mass rate of SARS-CoV-2 RNA in the wastewater to predict the number of infected individuals, and have also provided a simplified equation to predict this. Model predictions were compared with the number of confirmed cases. We found that the SEIR model provides a robust method to estimate the total number of infected individuals in a sewershed on the basis of the mass rate of RNA copies released per day.

Based on data collected till December 7, 2021, we showed the exponential growth of the Omicron variant over the four-week period in Gauteng (November 8-December 5, 2021) with the doubling time equal 3.38 day [CI 95%: 3.18-3.61 day]. Log-linear regression suggests that the spread began around October 10, 2021, however due to stochasticity in the initial spread this estimate is likely inaccurate. Phylogenetic analysis indicates that the Omicron strain started to diverge in between October 28 and November 5, 2021. This implies that the hidden spread of Omicron before October 10, 2021 (which would suggest slower strain growth) is unlikely. The very short doubling time of Omicron in Gauteng, a province that has reached herd immunity to the Delta variant suggests that Omicron will cause abrupt outbreaks of COVID-19 epidemics across the world, and will become the (temporarily) dominant strain.

Using a broad PheWAS approach in a large discovery and validation cohort, we have identified novel phenotypic associations with risk alleles for severe COVID-19 infection. Interestingly, the ABO locus was associated with comorbidities that are also risk factors for severe COVID-19 infection, suggesting that this locus has pleiotropic effects and provides a potential mechanism for this association. The 19p13 locus was associated with lower risk of autoimmune disease, these findings may have broad implications for the importance of multiple comorbidities across both infectious and non-infectious diseases and may provide insight in the molecular function of the genes near these genetic risk loci.

We used national population data to estimate the household transmissibility of the SARS-CoV-2 lineage B.1.1.7 compared with other lineages. We utilized detailed administrative register data comprising the full Danish population and the ability to link data across registers on a person level. This combined with a large proportion of the population being tested, a large national WGS capacity, and an understanding of the sampling selection process, allowed us to estimate the household transmissibility controlling for age and viral load. We found that B.1.1.7 had a household transmissibility 1.5–1.7 times higher compared with other lineages circulating at the time of the study.

Using isolates of SARS-CoV-2 WT, Beta, Delta and most importantly Omicron we studied the capability of the BNT162b2 vaccine given in two or three doses to neutralize major SARS-CoV-2 variants of concern (VOC). We demonstrate low neutralization efficiency against delta and wild-type for vaccines with more than 5 months following the second BNT162b2 dose, with no neutralization efficiency against Omicron. We demonstrate the importance of a third dose, by showing a 100-fold increase in neutralization efficiency of Omicron following a third dose, with a 4-fold reduced neutralization compared to that against the Delta VOC. The durability of the effect of the third dose is yet to be determined.

Given omicron potential to escape vaccine-induced humoral immunity, we measured neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-12 months), or recently boosted, and accounted for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinated individuals. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is significantly more infectious than any other variant tested.

We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1?million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28?days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1?million vaccinated in the 28?days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1?million patients in the 28?days following a SARS-CoV-2 positive test.

We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunization with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. We found that primary immunization with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.

We show that, with first-generation SARS-CoV-2 vaccines and limited physical distancing in place, the threshold for Omicrons future dominance will primarily be driven by its degree of infectivity. However, Omicrons potential dominance may not necessarily lead to increased public health burden. Expanded vaccination that includes a third-dose for adults and child vaccination strategies is projected to have the biggest public health benefit for a highly infective, highly severe variant with low immune evasion capacity.

This is a wastewater-based epidemiology study using wastewater samples that were collected weekly or twice a week from three sewersheds in South Carolina, USA, between either May 27 or June 16, 2020, and Aug 25, 2020, and tested for SARS-CoV-2 RNA. We developed a susceptible-exposed-infectious-recovered (SEIR) model based on the mass rate of SARS-CoV-2 RNA in the wastewater to predict the number of infected individuals, and have also provided a simplified equation to predict this. Model predictions were compared with the number of confirmed cases. We found that the SEIR model provides a robust method to estimate the total number of infected individuals in a sewershed on the basis of the mass rate of RNA copies released per day.

Based on data collected till December 7, 2021, we showed the exponential growth of the Omicron variant over the four-week period in Gauteng (November 8-December 5, 2021) with the doubling time equal 3.38 day [CI 95%: 3.18-3.61 day]. Log-linear regression suggests that the spread began around October 10, 2021, however due to stochasticity in the initial spread this estimate is likely inaccurate. Phylogenetic analysis indicates that the Omicron strain started to diverge in between October 28 and November 5, 2021. This implies that the hidden spread of Omicron before October 10, 2021 (which would suggest slower strain growth) is unlikely. The very short doubling time of Omicron in Gauteng, a province that has reached herd immunity to the Delta variant suggests that Omicron will cause abrupt outbreaks of COVID-19 epidemics across the world, and will become the (temporarily) dominant strain.

Using a broad PheWAS approach in a large discovery and validation cohort, we have identified novel phenotypic associations with risk alleles for severe COVID-19 infection. Interestingly, the ABO locus was associated with comorbidities that are also risk factors for severe COVID-19 infection, suggesting that this locus has pleiotropic effects and provides a potential mechanism for this association. The 19p13 locus was associated with lower risk of autoimmune disease, these findings may have broad implications for the importance of multiple comorbidities across both infectious and non-infectious diseases and may provide insight in the molecular function of the genes near these genetic risk loci.

We used national population data to estimate the household transmissibility of the SARS-CoV-2 lineage B.1.1.7 compared with other lineages. We utilized detailed administrative register data comprising the full Danish population and the ability to link data across registers on a person level. This combined with a large proportion of the population being tested, a large national WGS capacity, and an understanding of the sampling selection process, allowed us to estimate the household transmissibility controlling for age and viral load. We found that B.1.1.7 had a household transmissibility 1.5–1.7 times higher compared with other lineages circulating at the time of the study.

Using isolates of SARS-CoV-2 WT, Beta, Delta and most importantly Omicron we studied the capability of the BNT162b2 vaccine given in two or three doses to neutralize major SARS-CoV-2 variants of concern (VOC). We demonstrate low neutralization efficiency against delta and wild-type for vaccines with more than 5 months following the second BNT162b2 dose, with no neutralization efficiency against Omicron. We demonstrate the importance of a third dose, by showing a 100-fold increase in neutralization efficiency of Omicron following a third dose, with a 4-fold reduced neutralization compared to that against the Delta VOC. The durability of the effect of the third dose is yet to be determined.

Given omicron potential to escape vaccine-induced humoral immunity, we measured neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-12 months), or recently boosted, and accounted for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinated individuals. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is significantly more infectious than any other variant tested.

We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1?million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28?days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1?million vaccinated in the 28?days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1?million patients in the 28?days following a SARS-CoV-2 positive test.

We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunization with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. We found that primary immunization with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.

We show that, with first-generation SARS-CoV-2 vaccines and limited physical distancing in place, the threshold for Omicrons future dominance will primarily be driven by its degree of infectivity. However, Omicrons potential dominance may not necessarily lead to increased public health burden. Expanded vaccination that includes a third-dose for adults and child vaccination strategies is projected to have the biggest public health benefit for a highly infective, highly severe variant with low immune evasion capacity.